Is there a link between acetaminophen (paracetamol) use and the development of autism?

Acetaminophen and Autism: Current Evidence and Recommendations

Based on the most recent and highest quality evidence, acetaminophen use during pregnancy is not associated with an increased risk of autism spectrum disorder in offspring when familial confounding factors are properly controlled. 1

Evidence Analysis

Current Medical Consensus

The Society for Maternal-Fetal Medicine (SMFM) and the American College of Obstetricians and Gynecologists (ACOG) have stated that the weight of evidence is inconclusive regarding a causal relationship between acetaminophen use during pregnancy and autism spectrum disorder 2. These organizations continue to recommend acetaminophen as a reasonable and appropriate medication choice for treating pain and fever during pregnancy.

Highest Quality Recent Evidence

The most recent and methodologically robust study (2024) published in JAMA examined 2,480,797 children born between 1995 and 2019 in Sweden 1. This nationwide cohort study with sibling control analysis found:

• Initial models without sibling controls showed marginally increased risks for autism (HR 1.05)
• However, when using matched sibling pairs to control for familial confounding factors, there was no evidence of association between prenatal acetaminophen exposure and:
  • Autism (HR 0.98,95% CI 0.93-1.04)
  • ADHD (HR 0.98,95% CI 0.94-1.02)
  • Intellectual disability (HR 1.01,95% CI 0.92-1.10)
• No dose-response relationship was observed in the sibling control analyses

This study's design specifically addressed the limitations of previous research by controlling for familial confounding factors that may have influenced earlier results.

Previous Research Findings

Earlier studies had suggested potential associations:

• A Danish birth cohort study (2016) found an association between acetaminophen use during pregnancy and ASD with hyperkinetic symptoms (HR 1.51,95% CI 1.19-1.92), particularly with longer duration of use (>20 weeks) 3
• A 2022 umbrella review noted possible associations between acetaminophen exposure and neurodevelopmental outcomes, with potential mechanisms involving the maternal immune system and fetal endocannabinoid system 4

However, these studies had important limitations:

• Many did not adequately control for confounding factors such as the underlying conditions requiring acetaminophen use
• Heterogeneity in study designs, exposure measurements, and outcome assessments
• Inability to fully account for familial factors that might influence both medication use and neurodevelopmental outcomes

Clinical Recommendations

1. For pregnant women:

   • Acetaminophen remains the safest medication option for necessary pain or fever relief during pregnancy 2
   • Use the lowest effective dose for the shortest possible time
   • Avoid prolonged use without periodic evaluation of continued need

2. For healthcare providers:

   • Discuss risks versus benefits with patients, emphasizing that the highest quality evidence does not support a causal link between acetaminophen use and autism
   • Consider that untreated pain or fever may pose greater risks to both mother and developing fetus
   • Exercise particular caution with prolonged use, especially in second and third trimesters

3. For parents concerned about postnatal exposure:

   • While some studies have suggested associations between postnatal acetaminophen exposure and ASD risk in males 5, these findings require further validation
   • Follow recommended dosing guidelines for children
   • Consider non-pharmacological approaches for mild pain when appropriate

Important Caveats

• The conditions requiring acetaminophen (fever, inflammation) may themselves contribute to neurodevelopmental outcomes 2
• Study quality varies significantly across the literature, with the most methodologically robust studies showing no association
• Acetaminophen remains widely used during pregnancy (40-65% of pregnant women) and is considered the safest analgesic/antipyretic option 2
• The potential risks of untreated pain or fever during pregnancy likely outweigh any theoretical risks associated with judicious acetaminophen use

The scientific consensus, supported by the most recent high-quality evidence, does not support avoiding acetaminophen during pregnancy due to concerns about autism risk.